This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Anogenital Human Papillomaviruses (HPVs) are the most common sexually transmitted pathogen and the primary cause of cervical cancer. The goal of this combined R21/R33 grant application is to screen for small molecules that can inhibit HPV infection, to identify related compounds with improved effectiveness, and to test the effectiveness of the most promising compound in a preclinical model for HPV infection. In the R21 Phase, a high throughput screen to identify candidate HPV-specific microbicides was accomplished. We screened a database of 4.5 million small molecules for ones with similar structures to those identified in the R21-phase screen and have identified the ten best candidate microbicides . We are now ready to start the R33 phase of this proposal with studies in a nonhuman primate model for anogenital HPV infection, based upon monitoring infection by Rhesus papillomavirus (RhPV1) in the reproductive tract of female Rhesus macaques. The feasibility of the studies proposed in this grant application rest upon our recently having developed a powerful and facile new technique for high yield production of infectious papillomaviruses. This breakthrough provides sufficient amounts of papillomavirus to allow one to screen for microbicides as well as to develop the RhPV1-based nonhuman primate model for anogenital papillomavirus infections.